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FLASH GENE

Symbol

IL1RL1

contributors: mct - updated : 24-02-2017

HGNC name	interleukin 1 receptor-like 1
HGNC id	5998

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	2q12.1      Physical location : 102.927.961 - 102.968.497
Synonym name	growth stimulation-expressed gene
	protein ST2
Synonym symbol(s)	MST2R, ST2V, ST2L, ST2, FIT1, DER4, FIT-1, T1, MGC32623, IL33R

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	40.54 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	two GATA motifs just upstream of the transcription start site in the promoter are critical for transcriptional activity
	possesses two promoters: the distal promoter functions in hematopoietic cells, including mast cells and basophils, and the proximal promoter is transactivated in fibroblasts

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D2S113 - D2S2187 - DNAJB2 - D2S2311 - D2S2264 - IL1RL2 - IL1RL1 - IL8RB - D2S373 - D2S299 - D2S135 - D2S176 - qter

regionally located

cluster of interleukin related genes (see map)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016232 11 - 2058 NP_057316 - 566 lung, testis, stomach, colon, spleen, kidney, placenta;helper Tcells.located in the plasma membrane, membrane bound 2014 24564816 also called IL1RL1B or ST2L motifs/domains : a large extracellular N terminal domain, including nine glycosylation sites and three Ig-like domains NM_003856 8 - 2542 NP_003847 - 328 stomach, small intestine, colon extracellular localization, soluble form 2014 24564816 also called IL1RILC or ST2V motifs/domains : extracellular domain with a short hydrophobic tail NM_001282408 7 - 3589 NP_001269337 - 211 - 2014 24564816

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Endocrine neuroendocrine pituitary     highly Nervous brain         Reproductive female system placenta     highly Respiratory lung       highly Visual eye anterior segment cornea     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune T cell not specific mast cell Homo sapiens Visual epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES		Hydrophobic
STRUCTURE

motifs/domains	IL1RL1A form : extracellular domain of IL1RL1
	IL1RL1B form : a large extracellular N terminal domain, including nine glycosylation sites and three Ig-like domains
	IL1RL1C form : extracellular domain with a short hydrophobic tail
	three Ig-like C2-type (immunoglobulin-like) domains
	a TIR domain

HOMOLOGY

interspecies	homolog to murine St2
	homolog to Drosophila CG10535

Homologene

FAMILY

interleukin-1 receptor family

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
text	soluble form
	selectively and stably expressed on the cell surface of T helper 2 (TH2) but not TH1 cells

basic FUNCTION	putatively involved in cell growth
	may be induced by proinflammatory stimuli, and may be involved in the function of helper T cells
	soluble IL1RL1 suppressed the signal transduction of lipopolysaccharide (LPS) and cytokine production in monocytic cells
	soluble IL1RL1 protein was internalized into dendritic cells, suggesting that soluble IL1RL1 protein acts by a noncanonical mechanism other than the sequestration of IL33
	IL33/IL1RL1 signaling plays an important role in regulating IL33 induced inflammatory responses in ocular surface
	involved in the initiation and perpetuation of inflammation
	cell-intrinsic role for the IL33/IL1RL1 axis in the regulation of apoptosis in mast cellls, identifying thereby a previously unappreciated pathway supporting expansion of the mast cellls population with inflammation
	IL33/IL1RL1 axis plays an essential role in the development of visceral adipose tissue Treg (VAT-Treg) cells
	IL33 and IL1RL1 function as a developmental switch to license thermogenesis during the perinatal period

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

	IL33/IL1RL1 pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGFA in tumor cells and attenuating tumor necrosis
	IL33/IL1RL1 signaling may be involved in periapical inflammation and tissue fibrosis

a component

INTERACTION

DNA

RNA

small molecule

protein	binding to ILR1LG
	GATA2 and GATA1 positively and negatively control human IL1RL1 gene transcription, respectively
	TMED1 associates with IL1RL1 (interaction mediated by the GOLD domain of TMED1 and the TIR domain of IL1RL1)
	IL33 signals through its ligand-binding primary receptor IL1RL1 and IL1 receptor accessory protein (IL1RAP)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in sera of SS (Sjogren Syndrome) patients and (Systemic Lupus Erythematosus) patients constitutional     --over   in patients with greater infarct transmurality and endocardial extent, and in the presence of microvascular obstruction constitutional     --over   elevated concentrations are predictive of sudden cardiac death in patients with chronic heart failure and provide complementary information to NT-proBNP levels constitutional     --over   IL33 and IL1RL1 positive cells were also significantly increased in Alzheimer disease (AD) brains when compared to non-AD brains

Susceptibility

to atopic dermatitis to mild preeclampsia

Variant & Polymorphism SNP	-26999A allele increase the risk of atopic dermatitis
	significantly increased mild preeclampsia risk was observed associated with GG genotype of rs1420103 polymorphisms

Candidate gene	serum levels of the soluble form serve as a biomarker for ventricular biomechanical strain and provide prognostic information in patients who have symptomatic heart failure (Kakkar 2009)
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular     IL33/IL1RL1 not only represents a promising cardiovascular biomarker but also a novel mechanism of intramyocardial fibroblast-cardiomyocyte communication that may prove to be a therapeutic target for the prevention of heart failure immunology inflammatory   blockade of IL1RL1 is a novel therapeutic strategy for familial hemophagocytic lymphohistiocytosis (FHL)

ANIMAL & CELL MODELS

Il1rl1 deletion increases inflammatory bone loss in experimental periapical lesions in mice